Chemokine is a collective term for basic heparin-binding proteins that have effects on leukocyte chemotaxis and leukocyte activation. Based on a comparison of the primary structures of various chemokines, the chemokines are classified into CXC, CC, C, and CX3C subfamilies according to the positions of conserved cysteine residues. XCL1 (also referred to as lymphotactin (Ltn) or lymphotactin α (Ltn-α)) and XCL2 (also referred to as lymphotactin β (Ltn-β)) are chemokines classified into the subfamily C described above. XCR1 (also referred to as GPR5, SCM-1α, or ATAC) is a G protein-coupled chemokine receptor, which specifically binds to XCL1 and XCL2.
Expression of XCR1 in various human tissues has been examined at the mRNA level. Expression of XCR1 is reportedly high in placenta, but low in spleen and thymus gland (NON PATENT LITERATURE 1). Further, XCR1 is mainly expressed in dendritic cells. In mice, XCR1 is highly expressed, particularly in CD8α+ dendritic cells (NON PATENT LITERATURE 2; and NON PATENT LITERATURE 3). The CD8α+ dendritic cells are normally present in secondary lymphoid tissues such as spleen and lymph nodes, and are known to perform “cross-presentation,” which serves an important role in reactions against infection and immunological responses to tumor cells. XCR1 is also known to be highly expressed in human CD141+ dendritic cells, which are considered to be homologues of mouse CD8α+ dendritic cells (NON PATENT LITERATURE 4).
Antigen taken up from the outside of cells into antigen-presenting cells is usually degraded into peptide, presented on class II major histocompatibility antigen (MHC class II), and recognized by CD4+ T-cells. In contrast, there is a case where the antigen taken up from the outside of cells is presented on class I major histocompatibility antigen (MHC class I) via a pathway different from the usual pathway described above. This antigen presentation process is referred to as “cross-presentation.” In this process, the antigen presented on MHC class I is recognized by the CD8+ T-cells, and then differentiated into cytotoxic T-cells (CTL) that play a role in phylaxis and the elimination of tumor cells in the host (Non Patent Literature 5).
Migration of various immune-related cells occurs during inflammation reaction. In particular, migration of dendritic cells to a local inflammatory site occurs for phagocytosis of antigens. Chemokines and chemokine receptors play important roles in causing such migration of dendritic cells. After migration to a local inflammatory site, the dendritic cells present antigens to T-cells, and activate T-cells. Subsequently, the information is transmitted from T-cells to many more immune-related cells, amplifying the immune reaction (Non Patent Literature 6).
Among antigen presenting cells, the dendritic cells have particularly excellent antigen-presenting ability, and play a very important role in the activation of the T-cells. It has been suggested that because T-cells are involved in the development and exacerbation of various immune diseases including autoimmune diseases, to control dendritic cells is to control the activation of T-cells, which may lead to the amelioration of various immune diseases (Non Patent Literature 6; and Non Patent Literature 7).
Further, it has been shown that a rabbit-derived polyclonal antibody against human XCR1 has an effect of inhibiting XCL-induced migration of normal oral keratinocytes and oral cancer cells (Non Patent Literature 8).